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Biomedical subjects

J Oertel

Publications and source records attributed to J Oertel.

At least 19 recordsLinked to original sources

Extended field radiotherapy, combined modality treatment or involved field radiotherapy for patients with stage IA lymphocyte-predominant Hodgkin's lymphoma: a retrospective analysis from the German Hodgkin Study Group (GHSG).

BACKGROUND: Since there are no randomized studies, the treatment of choice for patients with early stage lymphocyte-predominant Hodgkin's lymphoma (LPHL) remains unclear. We thus reviewed all LPHL cases registered in the database of the German Hodgkin Study Group (GHSG) and compared the different treatment approaches, such as extended field (EF), involved field (IF) radiation and combined modality (CM) treatment for LPHL stage IA patients. PATIENTS AND METHODS: One hundred and thirty-one patients with LPHL in clinical stage IA without risk factors were analyzed. Forty-five patients were treated with EF radiotherapy, 45 patients with IF radiation and 41 patients received CM treatment. The median follow-up was 78 months in the EF group, 40 months after CM and 17 months after IF, respectively. RESULTS: A total of 129 patients achieved complete remission (CR and CRu): 98% after EF radiotherapy, 100% after IF radiation and 95% after CM. With a median follow-up of 43 months there were 5% relapses and only three patients died. Toxicity of treatment was generally mild with most events observed after CM. CONCLUSION: In terms of remission induction IF radiotherapy for stage IA LPHL patients is as effective as EF or CM treatment. However, longer follow-up is needed before final conclusion as the optimal therapy.

Adolescent↗

Limitations of dorsal transpedicular stabilization in unstable fractures of the lower thoracic and lumbar spine: an analysis of 133 patients.

The optimal treatment of thoracic and lumbar fractures remains controversial. While many authors recommend dorsal instrumentation with an internal fixator, others favour an anterior approach. To evaluate the posterior approach and to identify conditions under which an anterior approach should be preferred, 133 patients with unstable thoracic and lumbar fractures of the spine who underwent dorsal instrumentation with an internal fixator were analyzed. Clinical data were recorded prospectively with respect to fracture type, neurological findings, operative complications, spinal deformation correction, and long-term outcome. All fractures were located between the 7th thoracic and the 5th lumbar vertebrae and were considered to be unstable with respect to the three column model. Seventy-six patients (57%) received surgery within the first seven days after the trauma. Postoperatively, 98% of patients with a radicular lesion or an incomplete transverse syndrome (47 patients, 35%) improved. Stable fracture consolidation after fixator removal was obtained in 98% (130 of 133 patients). The preoperative kyphosis angle decreased from an average of 10.1 degrees to 7.4 degrees at the three year follow up. Major operative complications consisted of two isolated nerve root lesions (1.5%), two deep wound infections with need of fixator removal (1.5%), and mallocation of two pedicle screws with need for another procedure in two patients (1.5%). Three patients (2%) suffered from insufficient bony fusion with increase of kyphotic deformation and required subsequent anterior stabilization. These three patients presented with an initial kyphosis or wedge angle of 20 degrees or higher. In conclusion, dorsal stabilization with the internal fixator is a safe and reliable treatment for unstable fractures of the lower thoracic and lumbar spine. The authors recommend this procedure because of its low-invasiveness in conjunction with satisfactory reconstruction and stabilization. However, an anterior approach should be considered in fractures with initial kyphotic deformation or wedge angle of 20 or more degrees.

Adolescent↗

Towards waterjet dissection in neurosurgery: experimental in-vivo results with two different nozzle types.

Waterjet dissection is under close investigation as a new neurosurgical tool. Experimentally, a precise tissue dissection with vessel preservation has been demonstrated in the porcine cadaver brain. The safety of the device has been shown in first clinical applications. However, a detailed in-vivo analysis of the waterjet device is still awaited. In the present study, two often applied nozzle types (100 microm diameter emitting a coherent straight jet; 120 microm diameter emitting a helically rotating jet) were experimentally studied in vivo. Forty-one rabbits received a frontal waterjet corticotomy on either side with one nozzle type after microsurgical removal of the arachnoid membranes. Animals were sacrificed at 1, 3, 7 days and 6 weeks after surgery. Dissection morphology and vessel preservation were evaluated. Tissue trauma was analyzed by the extent of intra-operative haemorrhage, postsurgical oedema formation and astrocytic as well as microglial reactions. In all animals, reliable brain dissection was observed. Macroscopically, only minor bleeding occurred. Microscopically, also very precise brain dissection with both nozzle types was found. Vessels were preserved with both pressures applied (5 and 10 bar). Dissections with the 100 microm straight nozzle were more precise with respect to dissection margins. However, no significant difference in vessel preservation and extent of haemorrhage, oedema formation, astrocytic and microglial reactivity was shown. Malfunction defined as clotting of the instrument occurred only with the 100 microm nozzle. In four 100 microm straight nozzle hemispheres, even no brain dissection was seen. The results indicate that the waterjet enables very precise and reliable brain parenchyma dissection with minimal trauma and vessel preservation in vivo. If this can be proven to be of clinical relevance, the instrument will become a valuable neurosurgical tool. Based on these results, the authors selected the 120 microm Helix nozzle for further research with this device in the CNS.

Animals↗

Fetal allogeneic dopaminergic cell suspension grafts in the ventricular system of the rat: characterization of transplant morphology and graft-host interactions.

Experimental transplantation trials of fetal cells in Parkinson's and Huntington's disease or multiple sclerosis still require allogeneic graft material and raise questions of graft rejection and immunosuppression. Alternatively to the striatum, the lateral ventricles have been discussed as grafting site in Parkinson's and Huntington's disease although little is known of the specific immunology of the ventricular system. To address this question, 28 adult female LEW1.W rats received intraventricular allogeneic dopaminergic cell suspension grafts from E14 DA rat fetuses. Twelve animals with syngeneic grafts served as control. Immunohistochemical examination was performed with staining for MHC expression, microglia-macrophages, various lymphocyte subsets, dopaminergic neurons and astrocytes at 4 days, and 1, 3, 6, and 12 weeks after transplantation. In all animals, intraventricular transplants were found, which showed maturation and integration in the host parenchyma at the later time points. Animals with allogeneic grafts developed a vivid immune response with strong MHC class I expression and dense lymphocyte infiltrates. Surprisingly, this immune response subsided at 12 weeks and healthy grafts remained. These results indicate (1) that, in contrast to intraparenchymal grafts, a strong immune response to allogeneic fetal cell suspension grafts can be elicited by intraventricular grafting, (2) that a peculiar immunological role of the ventricular system has to be considered in further studies, and (3) that a vivid immune response to allografts in the brain may subside without graft destruction.

Animals↗

Treatment of advanced Hodgkin's disease with COPP/ABV/IMEP versus COPP/ABVD and consolidating radiotherapy: final results of the German Hodgkin's Lymphoma Study Group HD6 trial.

BACKGROUND: The purpose of this study was to compare the efficacy of the hybrid chemotherapeutic regimen COPP/ABV/IMEP (cyclophosphamide-vincristine-procarbazine-prednisone-doxorubicin-bleomycin-vinblastine-ifosfamide-methotrexate-etoposide) (CAI) with that of the standard regimen COPP/ABVD (COPP/ABV, dacarbacine) (CA) in the treatment of advanced-stage Hodgkin's disease (HD). PATIENTS AND METHODS: Between January 1988 and January 1993, 588 eligible patients with HD in stages IIIB and IV were randomly assigned to a treatment or control group. The treatment group received four cycles of CAI over a complete cycle duration of 43 days. The control group received four cycles of CA over 57 days. Both groups then received consolidating radiotherapy. RESULTS: Five hundred and eighty-four patients were suitable for arm comparison. Patients in each group were similar in age, sex, histological subtype and clinical risk factors. Complete remission rates, overall survival and freedom from treatment failure at 7 years were similar for the two groups: 77% versus 78%, 73% versus 73% and 54% versus 56% for CAI and CA, respectively. Differences in acute chemotherapy-related toxicity were significant, however. Prognostic factor analysis confirmed the relevance of the International Prognostic Index and revealed that stage IVB, low hemoglobin, low lymphocyte count, high age and male gender were associated with a poor prognosis CONCLUSION: The rapidly alternating hybrid CAI did not give superior results when compared with the standard regimen CA in advanced-stage HD.

Adolescent↗

Cytomegalovirus infections in allogeneic stem cell recipients after reduced-intensity or myeloablative conditioning assessed by quantitative PCR and pp65-antigenemia.

Since the incidence of cytomegalovirus (CMV) infections after hematopoietic stem cell transplantation (HSCT) may depend on the intensity of the pretreatment, we studied the incidence of CMV infections after reduced-intensity compared to myeloablative conditioning. A total of 82 patients with matched related or unrelated donors were prospectively monitored for CMV infections after HSCT by CMV-PCR techniques, CMV-antigenemia and clinical observation. A total of 45 patients received reduced-intensity conditioning consisting of fludarabine, busulfan and ATG and 37 patients received myeloablative conditioning. Leukocyte engraftment occurred after a median of 15 vs 18 days (P=0.012) and platelet engraftment after 12 days vs 20 days (P=0.001), respectively. Acute graft-versus-host disease (GVHD) grade II-IV was observed in 58 vs 54% patients (P=0.737), respectively. The onset and peak values of CMV-antigenemia and DNAemia and the incidence of CMV infections did not differ statistically significantly between the two treatment groups. Multivariate analysis confirmed CMV seropositivity of the recipient (P=0.035), acute GVHD II-IV (P=0.001) but not the type of conditioning as significant risk factors for CMV-antigenemia. In conclusion, the kinetics of CMV-antigenemia and DNAemia and the incidence of CMV infections were not statistically different in patients who received HSCT after reduced-intensity conditioning with fludarabine, busulfan and ATG compared to myeloablative conditioning.

Adolescent↗

Waterjet resection of brain metastases - first clinical results with 10 patients.

The waterjet technique enables precise tissue dissection without thermal damage and with preservation of vessels in general surgery. In neurosurgery, these qualities could help to avoid damage of intact brain parenchyma in tumour resections. The present study reports our first results with this technique in brain metastases. Ten patients with intracranial metastases underwent surgery with the aid of the waterjet. Resection was performed in combination with conventional neurosurgical methods. The follow-up consisted of neurological examination and MRI studies. Intraoperatively, the device was easy to handle. No complications due to the device were observed. Vessels were preserved at pressures below 20 bars. Six of the tumours consisted of soft tissue which was poorly demarcated from the surrounding brain. In these tumours, the waterjet was very helpful. It enabled tumour debulking by aspiration and - more important - precise separation of tumour and brain parenchyma. The remaining four cases were rather hard and well demarcated metastases. In these only separation of the tumour from the surrounding brain was achieved. In conclusion, the waterjet can be applied in surgery of brain metastases without complications. The device appears particularly suitable for soft, poorly demarcated metastases. Further clinical studies with this device are required.

Brain Neoplasms↗

Morphologic diagnosis of leukaemic B-lymphoproliferative disorders and the role of cyclin D1 expression.

PURPOSE: This study analysed the morphologic differences between leukaemic mantle cell lymphoma, follicular lymphoma, nodal marginal zone lymphoma, and diffuse large B-cell lymphoma in peripheral blood. Additionally, we investigated the role of cyclin D1 expression in B-lymphoproliferative disorders. METHODS: The morphologic analysis of the leukaemic cells was performed on cytocentrifuge preparations after separation of mononuclear cells from peripheral blood using a Ficoll-Hypaque density gradient. Cyclin D1 protein expression was studied with the catalyzed signal amplification system. The expression of other markers (CD5, CD23, light chain immunoglobulins) was analysed by the APAAP method. RESULTS: We describe in detail the morphology of the lymphoma cells in eight patients with mantle cell lymphoma, six patients with follicular lymphoma, 11 patients with nodal marginal zone lymphoma, and seven patients with diffuse large B-cell lymphoma. The morphological distinction between these lymphoma cells is a challenge for the haematologist. The investigation of cytocentrifuge preparations of mononuclear cells allows the detection of lymphoma cells also in cases with nondiagnostic white cell differential. Additionally, the immunotype (light chain restriction, CD5, CD23, and cyclin D1) of 108 patients with leukaemic B-lymphoproliferative disorders was studied. Diffuse nuclear expression of cyclin D1 protein (>20%) was specific for mantle cell lymphoma. However, only 6/8 patients showed cyclin-D1 positivity. CONCLUSIONS: The morphologic analysis of lymphoma cells in cytocentrifuge preparations of mononuclear leukocytes in combination with immunocytochemical investigation allows the detection of mantle cells, centrocytes of follicular lymphoma, marginal zone cells, and cells of the diffuse large B-cell lymphoma in peripheral blood. The positivity of cyclin D1 protein improves the differentiation of mantle cells from other lymphoma cells.

Biomarkers, Tumor↗

Detection of small numbers of cells characteristic for haematological disorders in peripheral blood (the deep diff).

We studied cytocentrifuge preparations of peripheral blood mononuclear leucocytes in haematological patients with nondiagnostic white cell differential counts. This approach (the 'deep diff') enabled the detection of small numbers of diagnostically significant cells in a majority of patients. We found ringed sideroblasts in 5/7 patients with sideroblastic anaemia and megaloblasts in 9/10 patients with megaloblastic anaemia. We observed centrocytes in seven patients with follicular lymphoma, mantle cells in five patients with mantle cell lymphoma and marginal zone cells in five patients with nodal marginal zone lymphoma. We detected small percentages of lymphoma cells in cytospins of mononuclear leucocytes in 12 patients with large B-cell lymphoma, Burkitt's lymphoma and anaplastic large-cell lymphoma. The deep diff was nondiagnostic in 5/6 patients with hairy cell leukaemia and in 9/10 patients with Waldenström's macroglobulinaemia and small lymphocytic lymphoma. In these cases, there were insufficient cells to detect light chain restriction. Increased counts of leukaemic cells were found in 12/13 patients with acute leukaemia with < 3% blasts in the conventional white cell differential. Increased blasts were also observed in six patients with refractory anaemia with excess of blasts (RAEB). Decreased blasts were found in five patients with aplastic anaemia and in nine patients with bone marrow aplasia after intensive chemotherapy. Increased plasma cell counts were observed in 13/14 patients with advanced plasma cell myeloma. We conclude that the 'deep diff', augmented by immunocytochemistry, may be useful in the diagnosis of haematological disorders.

Anemia↗

Immunocytochemical methods in haematology and oncology.

Immunocytochemical investigations of fixed cells are used to enhance diagnostic accuracy in haematology and oncology. The alkaline-phosphatase/anti(alkaline phosphatase) technique, immunoperoxidase and the avidin-biotin technique are the most important methods in immunocytochemistry. Tyramide-enhanced immunostaining is a new powerful technique. Peripheral blood smears and cytospins of mononuclear blood leucocytes have been analysed with this technique and these methods are also useful for analysis of bone marrow, cerebrospinal fluid, serous effusions and fine-needle aspirates. This review describes the results of immunocytochemistry in patients with B- and T-lymphoproliferative disorders, acute leukaemias and Hodgkin's disease. These methods are also useful for the detection of epithelial malignant cells. Immunocytochemistry supports the morphological analysis of cells in these disorders.

Bone Marrow Cells↗

Automated collection of peripheral blood stem cells with the COBE spectra for autotransplantation.

BACKGROUND: A convenient, effective and safe peripheral blood stem cell (PBSC) apheresis procedure is desirable to cope with the increasing requirements for PBSC collections. We performed PBSC harvesting with the novel COBE Spectra AutoPBSC(TM) system using the default software configuration recommended by the manufacturer. We analyzed collection parameters and clinical efficiency of harvested autografts following high-dose chemotherapy (HDCT). PATIENTS AND METHODS: Eighty-one patients underwent 102 harvests after standard chemotherapy plus filgrastim (5-10 microg/kg/day) to obtain a target of >/=2.5 x 10(6) CD34+ cells/kg for autologous blood stem cell transplantation. Conventional-volume leukaphereses (median: 11 liters) were performed using the manufacturer's standard software default regarding inlet flow, harvest/chase volume (3/7 ml) and number of collection cycles. The ratio of ACD-A to whole blood was initially set at 1:12 (56 collections), later at 1:10 (46 aphereses). RESULTS: With respect to preapheresis counts of 93 (9-876) CD34+ cells/microl, 69 patients (85.2%) achieved >/=2.5 x 10(6) CD34+ cells/kg by the first apheresis. PBSC products contained medians of 5.0 x 10(6) (0.7-77.3) CD34+ cells/kg and 13.8 x 10(4) (2.3-105.0) CFU-GM/kg. A preapheresis count of >/=40 CD34+ cells/microl predicted a single-apheresis yield of >/=2.5 x 10(6) CD34+ cells/kg. Apheresis products showed a high mononuclear cell (MNC) purity of >/=89%. The median overall collection efficiency of CD34+ cells (CD34-CE) was 42.6% (12.2-87.4). The CD34-CE decreased significantly with increasing numbers of circulating CD34+ cells: 52.5% at CD34+ cells <40/microl versus 41.0% at CD34+ cells >/=40/microl (p </= 0. 002). Coagulation problems occurred in 3 of 56 procedures at an ACD-A to whole blood ratio of 1:12, but in no case at 1:10. Patients who underwent HDCT and autologous blood stem cell transplantation (n = 40) engrafted in a median time of 9 (8-13) days for absolute neutrophil counts >0.5 x 10(3)/microl, 10 (8-13) days for WBC >1.0 x 10(3)/microl and 11 (8-17) days for platelets >20 x 10(3)/microl. CONCLUSIONS: As a result of efficient PBSC mobilization, a single conventional-volume leukapheresis with the COBE Spectra AutoPBSC system resulted in hematopoietic autografts with >/=2.5 x 10(6) CD34+ cells/kg in 85% of patients. Following the standard PBSC apheresis recommendations of the manufacturer, the AutoPBSC system assures PBSC products with a high MNC purity and a moderate CD34-CE that declines significantly at increasing levels of circulating CD34+ cells. Leukaphereses performed at an ACD-A to whole blood ratio of 1:10 should run without coagulation problems.

Adolescent↗

Norepinephrine stimulates lymphoid cell mobilization from the perfused rat spleen via beta-adrenergic receptors.

The possibility that norepinephrine (NE) influences lymphoid cell outflow independently of its vasoconstrictor action was investigated in the perfused rat spleen. Using agents that affect the vasoconstrictor tonus of the spleen, we observed an inverse correlation between flow resistance and splenic cell output. The curve obtained served as a reference for evaluating effects of different treatments on the number of cells that are mobilized at defined levels of flow resistance. Perfusion of the beta-adrenergic blocker propranolol either alone or in combination with NE lowered splenic leukocyte outflow clearly beyond the number of cells expected at the corresponding flow resistance. No comparable effects were observed when the alpha-adrenergic blocker phentolamine was perfused. When the vasoconstrictor effect of NE was counteracted by papaverine, splenic cell outflow was significantly higher than expected for the level of flow resistance attained. Furthermore, when NE was perfused together with endotoxin, which does not inhibit the vasoconstriction induced by catecholamines, splenic cell mobilization was severalfold higher than expected at increased flow resistance. Propranolol abrogated this effect to a large extent. Furthermore, perfusion of the beta-agonist isoproterenol stimulated lymphoid cell outflow from the spleen despite increased flow resistance. These studies show a dual effect of NE on cell mobilization from the spleen: cell retention by decreasing blood flow and stimulation of cell output by a beta-adrenergically mediated, smooth muscle-independent mechanism.

Animals↗

Detection of small numbers of immature cells in the blood of healthy subjects.

AIMS: To determine the frequency of immature haemopoietic cells in the peripheral blood of healthy persons. METHODS: Cytocentrifuge preparations were made using mononuclear leucocytes separated by a Ficoll-Hypaque density gradient. The slides were stained by May-Grünwald-Giemsa. The combination with immunoperoxidase technique allowed immunotyping of uncommon blood cells. RESULTS: Blast cells expressing the progenitor cell marker CD34 represented 0.11 (0.06) per cent (mean (SD)) of the total mononuclear leucocyte count; these were the haemopoietic progenitor cells in the peripheral blood. Dark blue cells expressing CD38, CD45, HLA-DR, CD4, CD11a, CD29, CD49d, CD50, and CD54 represented 0.30 (0.21) per cent of the mononuclear leucocytes; most of these cells did not express T, B, NK, myelomonocytic, progenitor cell, proliferation, activation, blood dendritic cell, or follicular dendritic cell markers. These were dendritic cell precursors in the peripheral blood. Very small numbers of cells expressing CD83 were found. Blast-like cells expressing CD45, HLA-DR, CD11a, and CD50 represented 0.15 (0.10) per cent of the mononuclear leucocytes; morphology and immunotyping supported the conclusion that these cells were poorly differentiated monocytes. CONCLUSIONS: Morphological investigation of mononuclear leucocytes in peripheral blood of healthy persons can be used to detect small numbers of blasts, dark blue cells, and blast-like cells. The immunoperoxidase technique can then be used for immunotyping of these cells. This simple method may be helpful in diagnosing haematological disorders.

Adult↗

Immunotyping of blasts in human bone marrow.

The diagnostic potential of immunocytochemical investigation of human bone marrow has not been fully realized due to difficulties in morphological identifying of immunostained cells. We used an indirect immunoperoxidase technique after May-Grünwald-Giemsa staining for simultaneous morphological and immunocytochemical analysis of blasts in human bone marrow. Six healthy bone marrow donors were investigated. Most blasts I expressed CD34, CD38 and HLA-DR. Expression of c-kit (CD117) was observed on 42 +/- 9% of blasts I. Granulocytomonocytopoietic character was demonstrated by expression of CD13 (33 +/- 15%) and CD45RA (23 +/- 10%) and erythropoietic character was demonstrated by expression of CD36 (22 +/- 8%) and CD45RO (30 +/- 11%). A very low proportion of blasts I were Thy-1 and CD61 positive; 34 +/- 6% of blasts I expressed CD22, representing B lymphoid committed progenitors. CD3, CD15, and glycophorin A expression was not detected. Blasts II and III and proerythroblasts did not show CD34 positivity. We conclude that blasts I are morphologically identifiable cells with a high percentage of CD34, CD38, and HLA-DR positivity. They are a pool of committed progenitor cells for erythropoiesis, granulocytomonocytopoiesis, megakaryocytopoiesis, and B cell development. Blast II and proerythroblast represent the first morphologically identifiable cells of granulocytopoiesis and erythropoiesis.

ADP-ribosyl Cyclase↗

Comparison of polymerase chain reaction from plasma and buffy coat with antigen detection and occurrence of immunoglobulin M for the demonstration of cytomegalovirus infection after liver transplantation.

We compared the value of PCR on plasma with PCR on buffy coat leukocytes, Ag assay, and the determination of IgM antibodies by ELISA for the diagnosis and follow-up of cytomegalovirus infection. Thirty patients were followed after liver transplantation (LTX). We compared the tests to assess their clinical usefulness. Fourteen of 30 (46%) patients were both positive in plasma and buffy coat PCR and Ag test. Sixteen patients were negative in both procedures. There was a 97.2% concordance between PCRs done from plasma or buffy coat. The concordance of results of PCR and Ag test in single samples was 94.3%. Discordant results were found in 5.6% of samples. Discordance was observed in the early and the late phase of CMV infection and was due to positive PCRs preceding positive Ag tests for 1-3 weeks in one-half of the patients. IgM antibodies were first observed after a median period of 8 weeks (range, 6-11 weeks) after LTX. Positive PCRs and Ag tests preceded clinical manifestation of CMV disease by a 1 week median (range, 0-3 weeks), whereas positive IgM ELISAs occurred after a median period of 2.5 weeks (range, 0-4 weeks) after the onset of CMV disease. The sensitivity and specificity of both PCR and Ag test were identical, 100% and 76%, respectively. However, for the IgM ELISA, the sensitivity was only 66%, and the specificity was 84%. In conclusion, plasma or buffy coat PCR and Ag test are equally reliable procedures for early detection and monitoring of CMV infection. PCR can become positive earlier than the Ag test, but it is technically more demanding to perform. The demonstration of IgM antibodies is of little practical help because an antibody response occurs too late in relation to infection.

Adult↗